Ketamine for Depression: Much Promise, Many Unknowns

In recent years, the potential use of ketamine to treat severe depression has generated a lot of hope and excitement and headlines. Ketamine has long been medically used as an anesthesia and misused as a street drug. It has also shown great promise in treating severe depression, but there are still many questions and potential concerns.

Emerging research has shown significant benefits of ketamine for depression. It works rapidly, in a matter of hours, while other depression medications take weeks to have an effect. This is particularly important when a person has severe depression and suicidal thoughts. Ketamine also works for many people who have not responded to other treatments. A meta-analysis appearing in the American Journal of Psychiatry in October last year found “compelling evidence that the antidepressant effects of ketamine infusion are both rapid and robust, albeit transient.”

Ketamine use for depression is off-label, meaning it has not been approved by the Food and Drug Administration for use in treating depression. Ketamine works differently that other antidepressants. It works on the neurotransmitter glutamate while most antidepressants developed during the 1980s work on the neurotransmitter serotonin. Ketamine for depression is usually delivered at a clinic through intravenous infusion, a process taking about 40 to 50 minutes.

Dennis Hartman participated in a National Institute of Mental Health clinical trial for ketamine in 2012. In a 2016 interview with Psychiatric News, he called his first experience with ketamine life changing. “I had suffered from depression for 35 years. I achieved remission within eight hours.” There are dozens of clinics around the country offering ketamine treatment, according to the Ketamine Advocacy Network, founded by Hartman to spread awareness about ketamine therapy.

In January, a Task Force of the American Psychiatric Association (APA)* issued a report providing an overview of ketamine and highlighting the unknowns and possible concerns. The beneficial effects of ketamine only last a short time, a few days to a week, requiring frequent treatments. There is only limited research on ketamine use for depression. The effects of long-term use have not been studied. The report notes that while large-scale clinical trials are not likely, there are several studies with federal and private foundation funding trying to address some of the questions. One additional concern is the potential for abuse and addiction.

Similar cautions are raised in an April 5 review and analysis in The Lancet. Researchers encourage development of guidelines for good practice and urge that experimental data be made widely available and that the risks of ketamine treatment continue to be monitored.

The APA report also emphasizes the importance of reporting on clinical practice and monitoring outcomes. They urge physicians, as part of an informed consent process, to discuss the risks associated with the treatment, the limits of information about risks, the fact that it is an off-label use and alternative treatment options. The report authors express desire to see the innovative use of ketamine for treatment-resistant depression to continue with “appropriate care, precaution, and foresight.”

*APA Council of Research, Task Force on Novel Biomarkers and Treatments